Site isolation and presentation of functionality are two key requirements for enzymatic catalysis. Researchers have developed synthetic systems that effectively mimic either the functionality or the isolation of enzyme active sites; creation of constructs that provide both of these attributes remains a significant challenge. We will use self-assembled monolayers (SAMs) on monolayer-protected gold clusters (MMPCs) to provide both the isolation and preorganization required to effectively replicate the behavior of flavoenzyme systems. There are three key thrusts to our proposed research: 1) The effective duplication of enzyme-cofactor interactions using the preorganization provided by the SAM, coupled with the control provided by the radial nature of the MMPC sidechains. 2) Fabrication of MMPC structures that provide effective isolation of cofactors buried within the SAM from solvent and other interfering species. 3) We will combine expertise gained from the above programs to design and fabricate fully functional mimics of the electron transferase family of flavoenzymes. These investigations will address key issues of recognition in water and control of enzyme mimic redox potentials, and will culminate with the creation of a functional electron shuttle designed to fully replicate the function of an electron transferase.